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Toxicological information

Basic toxicokinetics

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Administrative data

Endpoint:
basic toxicokinetics in vivo
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Study period:
Not reported
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: This study was classified as reliable with restrictions. The study is an acceptable, well-documented study report that followedsound scientific principles.

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1996

Materials and methods

Principles of method if other than guideline:
The method did not strictly follow the guideline but is deemed appropriate as utilized in this report.
Fischer-344 rats of each sex were fed control diet or diet containing one of 5 waxes for 90 days at a dietary concentration of 2.0%. Extra groups of rats (5 of each sex) were fed control diet or one of the 5 waxes for 90 days followed by exposure to control diet only for an additional 28 or 85 days. These extra groups were used to determine whether effects were reversible.
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Type:
Constituent
Type:
Constituent
Test material form:
other: waxy solid
Details on test material:
- Name of test material (as cited in study report): low melting point paraffin wax
- Substance type: paraffin wax
- Physical state: solid
- Viscosity at 100°C: 3.3 cSta
- Average molecular weight: 375
-Average carbon number distribution: 19-42

- Name of test material (as cited in study report): 1:1 mix of low melting point wax, paraffin and high melting point wax, microcrystalline
- Substance type: paraffin wax and microcrystalline wax mix
- Physical state: solid
- Viscosity at 100°C: 7.2 cSta
- Average molecular weight: 305
-Average carbon number distribution: 19-72

- Name of test material (as cited in study report): intermediate melting point wax, paraffin
- Substance type: paraffin wax
- Physical state: solid
- Viscosity at 100°C: 6.3 cSta
- Average molecular weight: 450
-Average carbon number distribution: 21-49

- Name of test material (as cited in study report): high sulphur wax
- Substance type: microcrystalline wax
- Physical state: solid
- Viscosity at 100°C: 13.7 cSta
- Average molecular weight: 600
-Average carbon number distribution: 20-74

- Name of test material (as cited in study report): high melting point wax
- Substance type: microcrystalline wax
- Physical state: solid
- Viscosity at 100°C: 15.4 cSta
- Average molecular weight: 630
-Average carbon number distribution: 22-80

The following applies to all five waxes:
- Analytical purity: not provided
- Impurities (identity and concentrations): no provided
- Composition of test material, percentage of components: not provided
- Isomers composition: not provided
- Purity test date: not provided
- Lot/batch No.: not provided
- Expiration date of the lot/batch: not provided
- Stability under test conditions: not provided
- Storage condition of test material: all test materials were stored in the dark at room temperature under an atmosphere of nitrogen
Radiolabelling:
no

Test animals

Species:
rat
Strain:
Fischer 344
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan sprague-dawley, Inc.
- Age at study initiation: 4 weeks
- Weight at study initiation: not provided
- Fasting period before study: no information provided
- Housing: five rats of each sex per cage
- Individual metabolism cages: no
- Diet (e.g. ad libitum): powered diet of rat and mouse no. 1 maintenance diet was provided ad libitum
- Water (e.g. ad libitum): tap water was provided ad libitum
- Acclimation period: seven days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 24°C
- Humidity (%): 45 to 70%
- Air changes (per hr): not provided
- Photoperiod (hrs dark / hrs light): 12 hours light and 12 hours dark


IN-LIFE DATES: not provided

Administration / exposure

Route of administration:
oral: feed
Vehicle:
unchanged (no vehicle)
Details on exposure:
PREPARATION OF DOSING SOLUTIONS: test diets of 20,000 ppm were prepared by serial dilution from 10% (100,00 ppm) premix. The samples of wax were solid and were first converted to a sprayed powder by drawing molten wax through an atomizer with a stream of liquid nitrogen.


DIET PREPARATION
- Rate of preparation of diet (frequency): fresh diets were prepared weekly
- Mixing appropriate amounts with (Type of food): rat and mouse No. 1 maintenance diet, Special Diet Services Limited, Witham, Essex
- Storage temperature of food: stored at room temperature and sealed in metal containers prior to use.


VEHICLE
- Justification for use and choice of vehicle (if other than water): none
- Concentration in vehicle: none
- Amount of vehicle (if gavage): none
- Lot/batch no. (if required): none
- Purity: none


HOMOGENEITY AND STABILITY OF TEST MATERIAL: confirmed analytically in study report
Duration and frequency of treatment / exposure:
Fischer-344 rats were fed control diet or diet containing one of 5 waxes for 90 days followed by exposure to control diet only for an additional 28 to 58 days. These extra groups were used to determine whether effects were reversible.
Doses / concentrations
Remarks:
Doses / Concentrations:
Rats were dosed 20,000 ppm of each of five waxes in their diet, equivalent to a dietary concentration of 2.0%.
No. of animals per sex per dose:
five animals per sex per dose
Control animals:
yes
Positive control:
none
Details on study design:
- Dose selection rationale: not provided
- Rationale for animal assignment (if not random): random
Details on dosing and sampling:
PHARMACOKINETIC STUDY (Absorption, distribution, excretion)
- Tissues and body fluids sampled: perirenal fat, kidney, liver, mesenteric lymph nodes, and spleen
- Time and frequency of sampling: not provided


Metabolite characterization studies were not preformed


Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on distribution in tissues:
Mineral hydrocarbons (MHC) were found in the livers, mesenteric lymph nodes (MLNs), and perirenal fat of all groups fed waxes; levels in the spleen and kidney were much less and did not exceed 0.1 mg/g tissue. Statistically significant increases of saturated hydrocarbon content in the liver were observed in groups fed waxes (LMPW, MP, and IMPW) except animals fed microcrystalline waxes (HSW and HMPW). Accumulation in the liver was greater in females than males. After a reversal period during which time the animals were fed control diet only, there was a lowering of MHC levels in both sexes with a greater reduction after the 85-day reversal period (80-90% reduction in females for the LMPW, IMPW, and MP waxes; not measured in males). The MLNs contained statistically significant increases of mineral hydrocarbons in the same treatment groups as for the liver. The MHC content in the MLNs was higher in females than males. There was little indication of any reduction in MHC of the MLNs after the 28-day reversal period. Data were not available for the 85 day-reversal groups. In samples of perirenal fat, the MHC content was increased to a similar extent in males and females fed LMPW. Although there was some evidence of a reduction in MHC levels after a 28-day reversal period, elevated levels nevertheless still remained.

Applicant's summary and conclusion

Conclusions:
MHCs were found in the livers, mesenteric lymph nodes (MLNs), and perirenal fat of all groups fed waxes; levels in the spleen and kidney were much less and did not exceed 0.1 mg/g tissue. Statistically significant increases of saturated hydrocarbon content in the liver were observed in groups fed waxes (LMPW, MP, and IMPW) except animals fed microcrystalline waxes (HSW and HMPW). Accumulation in the liver was greater in females than males. After a reversal period during which time the animals were fed control diet only, there was a lowering of MHC levels in both sexes with a greater reduction after the 85-day reversal period (80-90% reduction in females for the LMPW, IMPW, and MP waxes; not measured in males). The MLNs contained statistically significant increases of mineral hydrocarbons in the same treatment groups as for the liver. The MHC content in the MLNs was higher in females than males. There was little indication of any reduction in MHC of the MLNs after the 28-day reversal period. Data were not available for the 85 day-reversal groups. In samples of perirenal fat, the MHC content was increased to a similar extent in males and females fedLMPW. Although there was some evidence of a reduction in MHC levels after a 28-day reversal period, elevated levels nevertheless still remained. 
Executive summary:
In a toxicokinetic study, five Fischer-344 rats of each sex were fed control diet or diet containing one of five microcrystalline or paraffin waxes (LMPW, HMPW, MP, HSW, IMPW) for 90 days at a dietary concentration of 2.0% or 20,000 ppm. Extra groups of rats (five of each sex) were fed control diet or one of the 5 waxes for 90 days followed by exposure to control diet only for an additional 28 or 85 days. These extra groups were used to determine whether effects were reversible.

 

MHCs were found in the livers, mesenteric lymph nodes (MLNs), and perirenal fat of all groups fed waxes; levels in the spleen and kidney were much less and did not exceed 0.1 mg/g tissue. Statistically significant increases of saturated hydrocarbon content in the liver were observed in groups fed waxes (LMPW, MP, and IMPW) except animals fed microcrystalline waxes (HSW and HMPW). Accumulation in the liver was greater in females than males. After a reversal period during which time the animals were fed control diet only, there was a lowering of MHC levels in both sexes with a greater reduction after the 85-day reversal period (80-90% reduction in females for the LMPW, IMPW, and MP waxes; not measured in males). The MLNs contained statistically significant increases of mineral hydrocarbons in the same treatment groups as for the liver. The MHC content in the MLNs was higher in females than males. There was little indication of any reduction in MHC of the MLNs after the 28-day reversal period. Data were not available for the 85 day-reversal groups. In samples of perirenal fat, the MHC content was increased to a similar extent in males and females fedLMPW. Although there was some evidence of a reduction in MHC levels after a 28-day reversal period, elevated levels nevertheless still remained. 

 

This study received a Klimisch score of 2 and is classified as reliable with restrictions.